Diabetes最新文献

{"title":"Erratum. 189-OR: Food Insecurity and Inability to Obtain Recommended Medications, Diabetes Technology, and Multidisciplinary Services in Youth and Young Adults with Diabetes. Diabetes 2024;73 (Suppl. 1):189-OR","authors":"Angela D. Liese, Emmanuel F. Julceus, Caroline Rudisill, Faisal Malik, Kate Flory, Edward A. Frongillo, Katherine A. Sauder, Jason A. Mendoza","doi":"10.2337/db24-er12b","DOIUrl":"https://doi.org/10.2337/db24-er12b","url":null,"abstract":"In the abstract cited above, author Nadine El Kalach was inadvertently omitted from the author list. The full, correct author list is as follows: Nadine El Kalach, Emmanuel F. Julceus, Caroline Rudisill, Faisal Malik, Kate Flory, Edward A. Frongillo, Katherine A. Sauder, Jason A. Mendoza, and Angela D. Liese. All authors approve the addition and the order of the revised author list. The authors apologize for the omission. The online version of the abstract (https://doi.org/10.2337/db24-189-OR) has been updated to correct the error.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"7 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GAS6 and AXL promote insulin resistance by rewiring insulin signaling and increasing insulin receptor trafficking to endosomes","authors":"Céline Schott, Amélie Germain, Julie Lacombe, Monica Pata, Denis Faubert, Jonathan Boulais, Peter Carmeliet, Jean-François Côté, Mathieu Ferron","doi":"10.2337/db23-0802","DOIUrl":"https://doi.org/10.2337/db23-0802","url":null,"abstract":"Growth-arrest specific 6 (GAS6) is a secreted protein that acts as a ligand for TAM receptors (TYRO3, AXL and MERTK). In humans, GAS6 circulating levels and genetic variations in GAS6 are associated with hyperglycemia and increased risk of type 2 diabetes. However, the mechanisms by which GAS6 influences glucose metabolism are not understood. Here, we show that Gas6 deficiency in mice increases insulin sensitivity and protects from diet-induced insulin resistance. Conversely, increasing GAS6 circulating levels is sufficient to reduce insulin sensitivity in vivo. GAS6 inhibits the activation of the insulin receptor (IR) and reduces insulin response in muscle cells in vitro and in vivo. Mechanistically, AXL and IR form a complex, while GAS6 reprograms signaling pathways downstream of IR. This results in increased IR endocytosis following insulin treatment. This study contributes to a better understanding of the cellular and molecular mechanisms by which GAS6 and AXL influence insulin sensitivity.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"79 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of BAF60b as a chromatin remodeling checkpoint of diet-induced fatty liver disease","authors":"Jing Zhong, Xiuyu Ji, Yali Zhao, Yihe Jia, Churui Song, Jinghuan Lv, Yuying Chen, Yanping Zhou, Xue Lv, Zhuoyin Yang, Zheyu Zhang, Qiyao Xu, Weihong Wang, Haiyan Chen, Aoyuan Cui, Yu Li, Zhuo-Xian Meng","doi":"10.2337/db24-0002","DOIUrl":"https://doi.org/10.2337/db24-0002","url":null,"abstract":"Overnutrition has gradually become the primary causative factor of nonalcoholic fatty liver disease (NAFLD). However, how nutritional signals are integrated to orchestrate the transcriptional programs important for NAFLD progression remains poorly understood. Here, we identified hepatic BAF60b as a lipid-sensitive subunit of the switch/sucrose-nonfermentable (SWI/SNF) chromatin-remodeling complex and is negatively associated with liver steatosis in mice and humans. Hepatic BAF60b deficiency promotes high-fat diet (HFD)-induced liver steatosis in mice, while transgenic expression of BAF60b in the liver attenuates HFD-induced obesity and NAFLD, both accompanied by a marked regulation of PPARγ expression. Mechanistically, through motif analysis of liver ATAC-Seq and multiple validation experiments, we identified CCAAT/enhancer-binding protein β (C/EBPβ) as the transcription factor that interacts with BAF60b to suppress PPARγ gene expression, thereby controlling hepatic lipid accumulation and NAFLD progression. This work uncovers hepatic BAF60b as a negative regulator of liver steatosis through C/EBPβ dependent chromatin remodeling.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"17 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1563-P: High Fat and Fructose Feeding Severely Impairs Hepatic Glucose Effectiveness but Not Insulin Action Under Euglycemic Conditions","authors":"DALE S. EDGERTON, GUILLAUME KRAFT, HANNAH L. WATERMAN, BEN FARMER, KALISHA YANKEY, MARTA S. SMITH, JON R. HASTINGS, MELANIE SCOTT, ALAN D. CHERRINGTON","doi":"10.2337/db24-1563-p","DOIUrl":"https://doi.org/10.2337/db24-1563-p","url":null,"abstract":"Diets high in fat and fructose (HFHF) disrupt glucose metabolism. This study compared the effects of a HFHF diet on liver insulin action vs glucose effectiveness. Dogs were fed either a chow or HFHF diet for 1 month. At the start of each study, 3-3H-glucose was infused and after a basal sampling period, somatostatin and basal glucagon were given. During the experimental period (4h) either insulin was infused into the hepatic portal vein at 4 fold basal, while glucose was delivered to maintain euglycemia (CHOW-INS and HFHF-INS), or glucose was infused to increase its level 2.5 fold, while insulin was maintained at basal (CHOW-GLC and HFHF-GLC) (n=6/grp). Plasma insulin, glucagon, glucose, and hepatic glucose load were matched within the respective groups. In response to selective hyperinsulinemia, net hepatic glucose balance (NHGB) was suppressed from output to uptake (basal period to last h; 1.2±0.1 to -1.0±0.2 vs 1.7±0.2 to 0.0±0.1; deltas of 2.2±0.2 vs 1.6±0.3 mg/kg/min in CHOW-INS vs HFHF-INS, respectively; p=0.2). Selective hyperglycemia, on the other hand, caused changes in NHGB of 1.1±0.2 to -2.5±0.4 vs 1.4±0.1 to 1.7±0.6; deltas of 3.6±0.4 vs -0.3±0.6 mg/kg/min in CHOW-GLC vs HFHF-GLC, respectively (p<0.001). Glucose turnover (Ra) was suppressed (basal period to last h) by 1.7±0.3 vs 1.3±0.1 mg/kg/min (p=0.4) in CHOW-INS vs HFHF-INS, and by 1.9±0.2 vs 0.5±0.1 mg/kg/min (p<0.001) in CHOW-GLC vs HFHF-GLC, respectively. Thus, the HFHF diet had a small, non-significant effect on liver insulin action under euglycemic conditions, whereas it severely impaired the effect of hyperglycemia in the presence of basal insulin (i.e. hepatic glucose effectiveness). These data demonstrate that the “gold standard” hyperinsulinemic euglycemic clamp may overlook substantial diet induced liver dysfunction. Furthermore, Ra accounts for glucose production but not liver uptake, thus has the potential to miss critical and substantial changes in liver glucose metabolism. Disclosure D.S. Edgerton: None. G. Kraft: None. H.L. Waterman: None. B. Farmer: None. K. Yankey: None. M.S. Smith: None. J.R. Hastings: None. M. Scott: None. A.D. Cherrington: Consultant; Abvance Therapeutics. Research Support; Abvance Therapeutics. Advisory Panel; AdipoPharma. Research Support; Cellular Longevity, Inc. dba Loyal. Advisory Panel; Fractyl Health, Inc. Consultant; Fractyl Health, Inc. Research Support; Fractyl Health, Inc. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Paratus, Portal Insulin. Advisory Panel; Sekkei Bio, Sensulin Labs, LLC. Consultant; Thetis Pharmaceuticals, LLC. Funding R01DK18243","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"24 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1971-LB: Contributions of Fasting and Postprandial Glucose Increments to Overall Hyperglycemia in Pregnant Women with Type 1 Diabetes","authors":"PING LING, DAIZHI YANG, CHAOFAN WANG, XUEYING ZHENG, SIHUI LUO, XUBIN YANG, HONGRONG DENG, WEN XU, JINHUA YAN, JIANPING WENG","doi":"10.2337/db24-1971-lb","DOIUrl":"https://doi.org/10.2337/db24-1971-lb","url":null,"abstract":"Aims: To evaluate the relative contribution of fasting hyperglycemia (FHG) and postprandial hyperglycemia (PHG) to overall hyperglycemia across time in range (TIR) and glycated hemoglobin (HbA1c) categories in pregnant women with type 1 diabetes mellitus (T1DM). Materials and Methods: This observational study included 112 pregnant women with T1DM from the CARNATION study who wore continuous glucose monitoring (CGM) devices during pregnancy. The data from CGM were analyzed for TIR, AUC of PHG, AUC of FHG, FHG and PHG contribution rates. The levels of HbA1c (<6.0, 6.0-8.0, ≥8.0%) and TIR(<60, 60-78,≥78%) were categorized according to the guidelines, and the contribution of FHG and PHG to the overall hyperglycemia were compared. Results: A total of 295 CGM-HbA1c profiles were analyzed in this study. All women experienced a mean TIR of 75.6±19.0% and a mean HbA1c of 6.2±1.1% during pregnancy. The FHG contribution rates increased gradually with TIR decreasing [74.9(36.8, 100) vs. 69.1(13.4, 100) vs. 66.5 (10.0, 100), P<0.001] or with HbA1c increasing [57.8% (0, 100) vs. 72.7% (36.8, 100) vs. 80.7% (31.4, 100), P<0.001], whereas the contribution of PHG decreased progressively with diabetes worsening. Conclusions: FHG was the major contributor to hyperglycemia during pregnancy. Along with controlling the postprandial hyperglycemia, pregnant women with T1DM who did not reach the target of TIR or HbA1c may benefit more from the optimization of insulin regimens focusing on reducing the fasting hyperglycemia. Disclosure P. Ling: None. D. Yang: None. C. Wang: None. X. Zheng: None. S. Luo: None. X. Yang: None. H. Deng: None. W. Xu: None. J. Yan: None. J. Weng: None. Funding Science and Technology Planning Project of Guangzhou (grant/award number: 202102010154), Diabetes mellitus research fund program from Shanghai Medical and Health Development Foundation (grant/award number: DMRFP_II_14 from SHMHDF).","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"160 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"138-OR: Pioglitazone Amplifies the Decrease in HbA1c and Prevents the Increase in Plasma Ketone Caused by Dapagliflozin in Type 1 Diabetes Mellitus Patients","authors":"MUHAMMAD ABDUL-GHANI, GOZDE BASKOY, AFIF NAKHLEH, SIHAM ABDELGANI, FAHD AL-MULLA, MOHAMED ABU-FARHA, FAHAD ALAJMI, THAMER ALESSA, RALPH A. DEFRONZO, NAIM SHEHADEH","doi":"10.2337/db24-138-or","DOIUrl":"https://doi.org/10.2337/db24-138-or","url":null,"abstract":"Introduction and Objectives: SGLT2 inhibitors (SGLT2i) lower the plasma glucose concentration in T1DM patients. However, they cause an increase in plasma ketone concentration and risk of ketoacidosis. The aim of the present study is to examine whether pioglitazone amplifies the decrease in HbA1c and prevents the increase in plasma ketone concentration caused by dapagliflozin in T1DM patients. Methods: After a 4-week run in period, 60 T1DM patients received dapagliflozin 10 mg for 12 weeks. At week 16 patients were randomized to receive in double blind fashion pioglitazone (45 mg) or matching placebo for an additional 16 weeks. Results: T1DM patients were 42±3 years of age, 30% female, BMI=26.8±0.7, HbA1c=8.5±0.2%, insulin dose= 63±4 units, and eGFR=114±6 ml/min. Dapagliflozin caused -0.63±0.18%, and -0.56±0.11% decrease from baseline in HbA1c at week 16 in subjects receiving pioglitazone and placebo, respectively (both p<0.001). At week 32, the decrease from baseline in HbA1c was -0.86±0.3 and -0.44±0.17 in subjects receiving pioglitazone and placebo, respectively. Thus, the HbA1c was -0.42±0.12 lower in subjects receiving pioglitazone versus placebo (p<0.05). Plasma ketone concentration increased above baseline by 0.12±0.03 mM and 0.14±0.03 mM at week 16 in subjects receiving pioglitazone and placebo, respectively (both p<0.05). At week 32 plasma ketone concentration remained elevated above baseline in subjects receiving placebo (0.15±0.03 mM, p<0.05), and decreased below baseline (-0.06±0.02mM, p<0.05) in subjects receiving pioglitazone. Thus, the difference in plasma ketone concentration between subjects receiving pioglitazone and placebo at week 32 was -0.19±0.3, p<0.001. Conclusion: Addition of pioglitazone to SGLT2i in T1DM patients amplifies the decrease in HbA1c and prevents the increase in plasma ketone caused by SGLT2i, allowing long-term cardiovascular and renal outcome studies to be carried out safely in T1DM patients. Disclosure M. Abdul-Ghani: None. G. Baskoy: None. A. Nakhleh: None. S. Abdelgani: None. F. Al-Mulla: None. M. Abu-farha: None. F. Alajmi: Consultant; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. T. Alessa: None. R.A. DeFronzo: Advisory Panel; AstraZeneca, Novo Nordisk, Boehringer-Ingelheim, Intarcia Therapeutics, Inc., Aardvark, Renalytix, Corcept Therapeutics, Alnylam Pharmaceuticals, Inc. Research Support; Boehringer-Ingelheim, AstraZeneca, 89bio, Inc., Amgen Inc., Medality, Corcept Therapeutics. Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Renalytix. N. Shehadeh: Research Support; Abbott. Advisory Panel; AstraZeneca, Eli Lilly and Company, Boehringer-Ingelheim. Research Support; Novo Nordisk Foundation. Funding The study was funded by JDRF grant to MAG. Astrazeneca provided dapagliflozin.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"35 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1666-P: Effect of Obesity in Family History (FH) on the Prevalence of Type 2 Diabetes Mellitus (T2DM), Hypertension (HT), and Dyslipidemia (DL)","authors":"IZUMI IKEDA, KAZUYA FUJIHARA, YASUNAGA TAKEDA, CHIKA HORIKAWA, SATORU KODAMA, EFREM D. FERREIRA, YASUMICHI MORI, TAKASHI KADOWAKI, RITSUKO YAMAMOTO-HONDA, YASUJI ARASE, HIROHITO SONE","doi":"10.2337/db24-1666-p","DOIUrl":"https://doi.org/10.2337/db24-1666-p","url":null,"abstract":"Heritability and obesity are strongly associated with the prevalence of T2DM, HT, and DL. We compared the effects of an FH of T2DM, HT, and DL combined with obesity on the prevalence of each in the same population. Of 41931 participants who underwent health checkups, the effects of an FH and BMI on the prevalence of those conditions were analyzed cross-sectionally. Prevalences of T2DM, HT, and DL were 5%, 20%, and 48%, respectively. Logistic regression analysis showed that ORs increased for all three as the number of FH positive cases increased and was most pronounced for T2DM. An FH of obesity and increased BMI were additively associated with the prevalence of the three diseases compared to BMI 20.0-21.9 and no positive FH (Fig. A). In addition, the combination of the number of family members with FH positivity (0,1, 2, ≥3) and obesity was additively associated with an increased FH of the three diseases compared to non-obesity and no FH of any of these diseases (Fig. B). For T2DM, the OR increased sharply in non-obese participants when the number of those with an FH of T2DM was ≥3 (14.4 [8.88-23.5]), but in obese participants the OR increased sharply when the number of those with an FH of T2DM was 2 (12.2 [8.85-16.9]) (Fig. B). Results suggest that, especially for T2DM, avoidance of obesity may be effective in reducing the prevalence of these disorders in those with many FH-positive family members. Disclosure I. Ikeda: None. K. Fujihara: None. Y. Takeda: None. C. Horikawa: None. S. Kodama: None. E.D. Ferreira: None. Y. Mori: None. T. Kadowaki: None. R. Yamamoto-Honda: None. Y. Arase: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"26 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1557-P: Increased PAHSA Hydrolysis Driven by Mutant Carboxyl Ester Lipase (CEL) Contributes to Beta-Cell Dysfunction in MODY8","authors":"ANNA SANTORO, SEVIM KAHRAMAN, GIORGIO BASILE, KHADIJA EL JELLAS, JIANG HU, RYAN TARPEY, BENTE B. JOHANSSON, ERCUMENT DIRICE, ISMAIL SYED, DIONICIO SIEGEL, ANDERS MOLVEN, BARBARA B. KAHN, ROHIT KULKARNI","doi":"10.2337/db24-1557-p","DOIUrl":"https://doi.org/10.2337/db24-1557-p","url":null,"abstract":"Maturity onset diabetes of the young type 8 (MODY8) is caused by genetic mutations in the CEL gene which is expressed primarily in pancreatic acinar cells. MODY8 patients develop pancreatic exocrine and endocrine dysfunction. How the enzymatic function of mutant (MUT) CEL contributes to the development of diabetes in MODY8 is unknown. Palmitic Acid Hydroxy Stearic Acids (PAHSAs) are signaling lipids that augment glucose-stimulated insulin secretion (GSIS). CEL is the major PAHSA hydrolytic enzyme in the pancreas. Aim: To determine whether CEL regulates insulin secretion and whether the increased PAHSA hydrolytic activity of MUT CEL contributes to MODY8 pathogenesis. Methods: We overexpressed wildtype (WT) or MUT CEL in acinar cells in vitro and in vivo. In vivo, we used 2 approaches both with AAV8 driven by an acinar cell specific promoter: intraductal AAV injections in wildtype mice and intraperitoneal AAV injections in CEL KO mice. CEL overexpression was detected exclusively in acinar cells. Results: 9-PAHSA augments GSIS in human pancreatic beta cells. Recombinant CEL inhibits the PAHSA effect. MUT CEL overexpression in acinar cells increases 9-PAHSA hydrolytic activity compared to WT CEL. In vivo, MUT CEL expression in acinar cells of wildtype mice markedly impairs glucose tolerance. In CEL KO mice, expression of MUT CEL in acinar cells impairs GSIS. Both WT and MUT CEL reduce total pancreatic PAHSA levels in CEL KO mice. However, 12/13-PAHSAs were reduced only with MUT CEL expression. Conclusions: 1) CEL in acinar cells alters PAHSA hydrolysis and modulates insulin secretion. 2) MUT CEL potentially contributes to the development of diabetes by increasing PAHSA hydrolysis and thereby limiting the normal PAHSA-induced augmentation of GSIS. 3) These data highlight the critical role of acinar-beta cell interactions and the physiologic role of PAHSAs in insulin secretion and provide opportunities for developing strategies to treat MODY8 and other forms of diabetes. Disclosure A. Santoro: None. S. Kahraman: Employee; Boehringer-Ingelheim. G. Basile: None. K. El Jellas: None. J. Hu: None. R. Tarpey: None. B.B. Johansson: None. E. Dirice: None. I. Syed: None. D. Siegel: None. A. Molven: None. B.B. Kahn: Advisory Panel; Janssen Pharmaceuticals, Inc. Consultant; Vida Ventures Advisors, Arrowhead Pharmaceuticals, Inc. R. Kulkarni: Advisory Panel; Novo Nordisk, Biomea Fusion, Inc. Consultant; Inversago Pharma. Advisory Panel; REDD Pharmaceutical. Funding K01 DK128075 (Anna Santoro), U01DK135095 (Rohit N. Kulkarni), R01DK067536 (Rohit N. Kulkarni), NIH R01 DK106210 (Barbara B. Kahn), JPB foundation (Barbara B. Kahn), and NIH P30 DK135043 (Barbara B. Kahn). Anna Santoro, Sevim Kahraman, Barbara B. Kahn and Rohit N. Kulkarni contributed equally.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"79 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1555-P: Effects of 80% Pancreas Reduction on Beta-Cell Function and Glucose Metabolism","authors":"LAURA SOLDOVIERI, GIANFRANCO DI GIUSEPPE, GEA CICCARELLI, MICHELA BRUNETTI, ANDREA MARI, GIUSEPPE QUERO, SERGIO ALFIERI, ANDREA GIACCARI, TERESA MEZZA","doi":"10.2337/db24-1555-p","DOIUrl":"https://doi.org/10.2337/db24-1555-p","url":null,"abstract":"Introduction and Objectives: Diabetes typically develops when the endocrine pancreas fails to cope to insulin demand with adequate insulin secretion. Many studies have shown that diabetes appears when the loss of pancreatic β cell mass is approximately between 41% and 65% in humans. Near total pancreatectomy (NTP) is a surgical procedure that removes 80% of pancreatic mass.To investigate the metabolic effects of NTP in a cohort of nondiabetic subjects. Methods: We recruited 7 subjects who underwent an oral glucose tolerance test (OGTT) and a hyperglycemic clamp (HC) followed by arginine stimulation, before and 3 months after NTP. We calculated the area under the curve of glucose (AUC-Glu) and insulin (AUC-Ins) responses during OGTT. Therefore, we estimated the β cell glucose sensitivity (βCGS), an index of β cell function, and rate sensitivity (RS), an index of first phase insulin secretion. Further, we calculated the total area under the curve of insulin responses (AUC-Itot) and the area under the of the arginine-stimulated insulin secretion (AUC-Arg) during HC. Results: Compared to presurgical OGTT, we observed a 18% increase in the mean glucose levels during OGTT after surgery (AUC-Glu 19761 vs 23421 mg/dl·min) with a 57% reduction of the mean insulin concentration (AUC-Ins 6499 vs 2788 μU/ml·min p<0.05). Further, we observed a 36% reduction βCGS (61.2 vs 38.7 pmol min-1m-2mmol-1L) and a 82% reduction in the RS (763 vs 139 pmol m-2mmol-1L p<0.05) after surgery. Both total insulin secretion and arginine-stimulated insulin secretion during HC were reduced (AUC-Itot 15776 vs 6489 μU/ml·min) (AUC-Arg 7144 vs 2520 μU/ml·min), respectively by 58.8% and 64.7%. According to the ADA diagnostic criteria 3 of the 7 subjects developed diabetes. Conclusion: In conclusion, despite previous reports, 80% β cell mass loss is not always sufficient to develop hyperglycemia. Additional studies will be necessary to understand what mechanisms play a compensating role in the preservation of glucose tolerance in those patients. Disclosure L. Soldovieri: None. G. Di Giuseppe: None. G. Ciccarelli: None. M. Brunetti: None. A. Mari: Consultant; Lilly Diabetes. G. Quero: None. S. Alfieri: None. A. Giaccari: None. T. Mezza: None.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"79 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"350-OR: Parturition Event Regulates Endocrine Genesis during Pancreas Differentiation","authors":"AGENA SUZUKI, TOMOMI TAGUCHI, SHIORI ITO, HIDEAKI SHIMOTATARA, KAORI KIMURA, NAOYA SHIMIZU, REI FUJISHIMA, MIWA HIMURO, TAKESHI MIYATSUKA","doi":"10.2337/db24-350-or","DOIUrl":"https://doi.org/10.2337/db24-350-or","url":null,"abstract":"It is essential to decipher developmental features of each endocrine cell, which leads to exploring efficient methods for generating surrogate β cells. We previously developed three reporter mouse lines to quantify the genesis of endocrine progenitor cells, β cells, and α cells. Flow cytometry analysis revealed a significant decrease in the number of newly-generated endocrine progenitors and β cells after birth. Based on these findings, we hypothesized that environmental changes during parturition could affect endocrine genesis. The number of newly-generated endocrine cells was quantified with the reporter mouse lines at the following stages: (i) embryonic day 19.5 (E19.5) embryos, whose parturitions were prolonged by progesterone or COX-1 inhibitor SC-560 vs. newborn pups at postnatal day 0.5 (P0.5) (both were dissected at 19.5 days after coitus), and (ii) premature pups treated with anti-progesterone drug RU-486 (both were at 18.5 days after coitus) vs. E18.5 embryos. Flow cytometry with Neurog3-Timer pancreata demonstrated that the percentage of green-fluorescent progenitors was (i) significantly higher in E19.5 embryos than in P0.5 pups (0.80% vs. 0.22%, p<0.001), and (ii) significantly lower in premature pups than in E18.5 embryos (0.66% vs. 0.93%, p=0.0018). Likewise, flow cytometry with Ins1-Timer pancreata resulted in a significant increase in β-cell genesis at E19.5 than at P0.5 (0.36% vs. 0.16%, p<0.001). Surprisingly, flow cytometry with Gcg-Timer mice resulted in (i) a significant decrease in α-cell genesis at E19.5 than at P0.5 (2.1% vs. 2.4%, p=0.035), and (ii) a significant increase in premature pups 18.5 days after coitus than in E18.5 embryos (0.77% vs. 0.58%, p=0.022), which is in contrast with the findings in Neurog3-Timer and Ins1-Timer pancreata. Thus, parturition events suppress the generation of endocrine progenitors and β cells, but not α-cell genesis, which may reflect distinct molecular mechanisms in α-cell lineage during parturition. Disclosure A. Suzuki: None. T. Taguchi: None. S. Ito: None. H. Shimotatara: None. K. Kimura: None. N. Shimizu: None. R. Fujishima: None. M. Himuro: None. T. Miyatsuka: None.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"2013 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}